Sulfate groups on complex sugar molecules affect brain plasticity

Are you able to recognize someone you have not seen in years, but forget what you had for breakfast yesterday? Our brains continually rearrange their circuitry to recollect familiar faces or learn recent skills, however the molecular basis of this process is not well understood. Today, scientists report that sulfate groups on complex sugar molecules called glycosaminoglycans (GAGs) affect “plasticity” within the brains of mice. Determining how GAGs function could help us understand how memory and learning work in humans, and supply ways to repair neural connectivity after injuries.

The researchers will present their results today at the autumn meeting of the American Chemical Society (ACS). ACS Fall 2023 is a hybrid meeting being held virtually and in-person Aug. 13–17, and features about 12,000 presentations on a wide selection of science topics.

The sugars that sweeten fruits, candies or cakes are literally just just a few easy varieties of the numerous kinds of sugars that exist. When strung together, they will make a wide selection of complex sugars. GAGs are formed by then attaching other chemical structures, including sulfate groups.

“If we study the chemistry of GAGs within the brain, we are able to find out about brain plasticity and hopefully, in the longer term, use this information to revive or enhance neural connections involved in memory,” says Linda Hsieh-Wilson, Ph.D., the project’s principal investigator presenting the research on the meeting.

“These sugars regulate quite a few proteins, and their structures change during development and with disease,” she explains. Hsieh-Wilson is on the California Institute of Technology.

Within the brain, essentially the most common GAG form is chondroitin sulfate, which is found throughout the extracellular matrix surrounding the brain’s many cells. Chondroitin sulfate also can form structures often known as “perineuronal nets,” which wrap around individual neurons and stabilize the synaptic connections between them.

A technique a GAG’s function could be modified is thru sulfation motifs, or patterns of sulfate groups tacked onto the sugar chains. Hsieh-Wilson’s team is considering how those sulfation patterns develop into altered, and the way they may regulate biological processes comparable to neuroplasticity and social memory. This might also sooner or later allow researchers to modulate these functions as a possible treatment for central nervous system injuries, neurodegenerative diseases or psychiatric disorders.

When the team deleted the Chst11 gene liable for forming two major sulfation patterns on chondroitin sulfate in mice, defects formed of their perineuronal nets. Nevertheless, the variety of nets actually increased within the absence of the sulfation motifs, changing the kinds of synaptic connections between neurons. As well as, the mice were unable to acknowledge mice that they’d previously been introduced to, which suggests that these patterns affect social memory.

Interestingly, these nets is likely to be more dynamic than once thought -; they might be playing a job in each childhood and maturity. When the researchers targeted Chst11 specifically within the brains of adult mice, they found the identical effects on perineuronal nets and social memory. “That result suggests that it might be possible to govern these nets during adolescence or maturity to potentially rewire or strengthen certain synaptic connections,” says Hsieh-Wilson.

In other recent experiments, the team wanted to grasp how GAGs and their sulfation patterns could affect axon regeneration, or the power of neurons to rebuild themselves after injury. The researchers are actually working to discover protein receptors that bind particular sulfation motifs. Thus far, they’ve found that specific motifs cause these receptors to cluster together on the cell’s surface and inhibit regeneration. This process might be blocked to create tools or treatments to advertise axon regeneration. Having more insight about this process could someday help repair damage brought on by certain neurodegenerative diseases or strokes, Hsieh-Wilson says.